The recent development of new neuroleptics that differ from the conventional neuroleptics in both mechanism of action and side-effects profile has introduced problems in their clinical assessment, and highlighted ongoing issues in the design and methodology of clinical trials. These issues are broadly grouped and discussed as follows: sampling problems and selection of patients; design issues; problems in measurement; ensuring compliance; recognition of extrapharmacological issues; and statistical models. For patients to benefit from the development of new neuroleptics, clinical settings have to be prepared for testing their efficacy and safety without too much delay in well designed clinical trials.

Remand prisoners diagnosed as psychotic by Holloway's psychiatrists were followed up to time of sentence. Most were referred to outside psychiatrists and then offered beds. Courts invariably enabled the beds to be used. Few women had committed serious offences, and most had been remanded because the courts thought they needed help. The study showed custodial remands to be an unsatisfactory way of seeking treatment for psychotic offenders. Alternatives need to be developed urgently. For psychotic people who continue to be remanded in custody, transfers rather than court orders should initially be used to effect admission.

We describe the limitations on studying the interactions of drugs of abuse in humans. Two ‘acute’ studies were carried out. In the first study, the administration of alcohol/placebo with cocaine showed the possibility of identifying the euphoric effect of the drugs by the EEG power spectra analysis in terms of enhancement of alpha- and beta-wave activity. The results of the second study, in which cocaine and buprenorphine were administered, show the existence of low-dose interactions and the influence of buprenorphine on craving for cocaine.

Two studies have been performed to evaluate the effect of activation tasks on neuroleptic-induced akathisia (NIA). In the first sample (30 patients) we found a consistent increase of symptoms during mental activation while motor activation led to a decrease. In a second study 34 patients with the same diagnosis were evaluated, using slightly different statistical procedures: while the effects of motor activation were corroborated, mental activation did not change NIA. Since mental and motor activation are usually considered to increase tardive dyskinesia and Parkinsonism, these measures might be helpful in differentiating NIA from other antipsychotic-induced movement disorders.

Treatment records of 94 patients treated in an experimental home-based psychiatric service and 78 control patients in standard care were collected over one year. There was a substantial reduction in in-patient care in the experimental group, both in terms of proportion admitted and duration of admissions, despite similar out-patient and general practice care. The total treatment costs were significantly larger (>50%) for standard care when controlled for by diagnostic grouping. Costs were further examined by including all specialist psychiatric care, and by excluding patients with primary diagnoses of brain damage or alcoholism. Sensitivity analysis explored the effects of increasing the cost of home visits. The relative cost effectiveness of the experimental service persisted. Clinical and social outcome was similar in control and experimental groups.

The use of items from the Schedule for Affective Disorders and Schizophrenia and from the Present State Examination scales for assessing positive and negative symptoms in schizophrenia was examined using factor analysis. The factorial structure of the items which putatively assess positive and negative symptoms was examined. A three-factor solution was obtained with factors identified as: a negative symptom factor (factor 1); a positive symptom factor (factor 2); a ‘disorganisation’ factor (factor 3), consisting primarily of items related to disordered thinking. A solution which was highly similar in important loadings was obtained with an independent sample of patients. High correlations of the rotated factors with the external criteria supported the interpretations of the factors. The results indicate that symptoms generally classified as negative or positive are factorially independent. Furthermore, a disorganisation factor, consisting of items previously included in positive and negative symptoms factors, is necessary for a full representation of the factor structure.

During Phase II of the Cross-National Panic Study, descriptions of the patient's last severe panic attack were collected for 1168 patients. Statistical analysis indicated that patients could be divided into two groups, characterised by the presence or absence of prominent respiratory symptoms. The two groups did not differ on demographic variables or coexisting diagnoses, but they did differ on psychopathology on entry to the study and treatment outcome. The group with prominent respiratory symptoms suffered more spontaneous panic attacks and responded to imipramine, whereas the group without prominent respiratory symptoms suffered more situational panic attacks and responded more to alprazolam. It is important to distinguish spontaneous and situational panic attacks, to aid choice of treatment.

Early-onset affective disorder is associated with obstetric complications and a high familial risk of psychiatric illness, in particular psychosis. In a matched case-control study, we investigated 47 adult in-patients with major depressive disorder or bipolar 1 disorder, who had earlier in life presented to a child psychiatry department. Cases were matched on sex, social class and ethnic group with 47 controls, who were admitted to hospital for affective disorders in adult life but had no psychiatric contact before the age of 21. We found that both psychiatric disorder in first-degree relatives and a history of obstetric complications were associated with early onset. Childhood symptoms did not predict the type of adult affective disorder.

This paper reviews the assumptions and efficacy of two strategies for dose reduction during maintenance treatment in schizophrenia: low dose and targeted medication. Studies of low-dose treatment suggest that it can be used for relatively short periods of time or if the dosage reduction is moderate. Studies of targeted treatment suggest that relapse risk increases significantly compared with standard-dose treatment and that there are few offsetting advantages. The paper also reports initial findings from the NIMH Treatment Strategies in Schizophrenia Study, which compares low dose, targeted treatment and a standard dose in the context of two forms of family treatment. Early stabilisation of patients is lower than expected, but patient characteristics are useful in predicting likelihood of stabilisation.

Twenty-five women with somatisation disorder (SD) were compared with matched patient controls for the presence of personality disorders. Personality was assessed with the Personality Assessment Schedule (PAS). Interviewers were unaware of the patients' diagnoses. All controls had DSM–III–R axis I diagnoses of depressive or anxiety disorders. The prevalence of personality disorders among patients with somatisation disorder was 72% compared with 36% among controls. Certain personality disorders, including passive–dependent, histrionic, and sensitive–aggressive, occurred significantly more often in the SD patients than controls.

Non-psychotic remand prisoners who were referred by Holloway's doctors to outside psychiatrists, or who were the subject of court reports, or who were diagnosed as mentally handicapped, were followed up to the time of sentence. Most of the referred women were minor offenders with diagnoses of mental handicap or personality disorder. They were usually refused beds on treatability criteria and then released with non-custodial sentences. Some were highly disturbed, and it seemed that the police who charged them, the courts who remanded them and the prison psychiatrists who referred them, all found it hard to accept that psychiatry had so little to offer these people. Local health and social services need to address the problems raised by this small group of women. Arsonists more often obtained beds than minor offenders, and were likely to be imprisoned when hospital places were not forthcoming.

Reports of childhood sexual experiences with adults were collected from 120 women attending general-practice surgeries and 115 women psychiatric patients. The method of study, research team and county of residence were the same for the two groups. The psychiatric patients tended to report rates of events higher than the general-practice attenders by a factor of 2–3. The results suggest an association between such experiences and later psychiatric patienthood and are compatible with a causal role for them in some cases.

Out of 24 spouses of women with postnatal psychiatric illness admitted to a mother and baby unit over 12 months, 12 were found to be psychiatrically ill, as defined by RDC or DSM-III criteria. The rate of psychiatric disorder was higher in these men than in a control group of men whose partners remained well after childbirth and a group of men whose partners were admitted to a psychiatric hospital with non-puerperal illness. The onset of psychiatric illness in the men typically followed admission of their wives to the mother and baby unit. Other associations with illness in the man were a history of chronic social problems, previous psychiatric episodes, and a poor relationship with his own father.

The Family Interpersonal Perception Test (FIPT) was used to explore the relationships between schizophrenic patients and their parents, and how these related both to relapse in the year after discharge and to improvement in social functioning. Forty schizophrenic patients and their parents were tested during their first ever admission to hospital and again two years later. Parents' and patient's views of each other were more negative in those with worse outcome, but what most significantly distinguished groups with different outcomes was how patients expected their parents to see them. The FIPT, therefore, reveals patterns of interaction in which the patient's role in outcome is at least as important as that of the parents, and can aid the identification of specific features with which to work in therapy.

Beyond the continuing use of neuroleptic medication, psychopharmacological treatment approaches during the maintenance phase of schizophrenia often involve adjunctive medication. Appropriate use of such ‘polypharmacy’ can be crucial to patients in achieving their optimal levels of symptom management and functional capacity, although the risks of side-effects and medication interactions must be weighed. This paper reviews the use of adjunctive anti-Parkinsonian medication, benzodiazepines, propranolol, antidepressants, lithium, and carbamazepine in this context. It also explores a strategy of identifying secondary syndromes in the longitudinal course of schizophrenia which can be approached psychopharmacologically.

The presence or absence of 22 schizophrenic symptoms was recorded with the age at onset of illness in 470 patients with non-affective, non-organic psychoses. Positive and negative formal thought disorder, affective symptoms, inappropriate affect, delusions of grandiosity or passivity, primary delusions other than delusional perception, and thought insertion and withdrawal were all more common in early-onset cases (age at onset 44 years or less; n = 336). Persecutory delusions with and without hallucinations, organised delusions, and third-person, running commentary and accusatory or abusive auditory hallucinations were all more common in late-onset cases (age at onset 45 years or more; n = 134). There was no difference between cases of early and late onset in the prevalence of delusions of reference, bizarre delusions, delusional perception, or lack of insight. We conclude that although there are clinical similarities between cases of schizophrenia with early and late onset, there are sufficient differences between them to suggest that they are not phenotypically homogeneous.

Psychiatry and psychopharmacology are no longer aiming to make a decisive breakthrough at the end of the century. Rather than seeking explanations, research workers are looking for ‘predictions’. Three main types of prediction are emerging: a tautological, a heuristic, and an irrelevant one. Few predictions found in the recent literature can be marked as ‘logical’ ones. Nevertheless, predictions play two important roles: they generate new hypotheses that can be falsified in properly designed scientific experiments; they also may serve to falsify given hypotheses. The main recent findings on predictions in psychiatry are briefly summarised.

A digital computer program generating a simulated neural network was used to construct a model which can show behaviour resembling human associative memory. The experimental network uses distributed storage, and, in this respect, its functional organisation resembles that suggested by reported observations of neuronal activity in the human temporal lobe during memory storage and recall. Inactivation of increasing numbers of randomly distributed network units simulated advancing cerebral atrophy. This caused progressive impairment of performance, resembling the gradual deterioration of memory function observed in chronic diffuse cerebral degeneration. Unit inactivation had similar effects on recall whether the same units were inactivated before or after learning. This differs from most relevant observations of amnesia resulting from diffuse cerebral disease. While the model may functionally resemble long-term information storage sites in the brain, other cerebral mechanisms participating in learning and remembering are also damaged by diffuse cerebral atrophy.